Asthma is a major cause of chronic morbidity and mortality, with an estimated 300million affected individuals worldwide and 250,000 annual deaths attributed to the disease. People of all ages in most countries are affected by this chronic disease.
Asthma is a chronic inflammatory disorder of the airways associated with airway hyper responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. An increased inflammatory response is a major part of the pathophysiology of acute asthma and regular preventive treatment of the same is very important.
Chronic obstructive pulmonary disease (COPD) is a severe respiratory condition that is increasing in prevalence worldwide. In India, the estimated prevalence is about 12.36 million.
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by air flow limitation that is not fully reversible. The airflow obstruction is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs it also produces significant systemic consequences. COPD is associated with mucus hyper secretion, emphysema and bronchiolitis.
Therapy for the treatment or prevention of COPD and asthma currently includes the use of bronchodilators and steroids.
More specifically asthma, COPD and other related disorders have been known to be treated with β2-agonists as they provide a bronchodilator effect, resulting in relief from the symptoms of breathlessness. β2-agonists can be short acting for immediate relief or long acting for long term prevention of asthma symptoms.
Long acting β2-agonists improve lung function, reduce symptoms and protect against exercise-induced dyspnea in patients with asthma and COPD. Long acting β2-agonists induce bronchodilation by causing prolonged relaxation of airway smooth muscle. In addition to prolonged bronchodilation, long acting β2-agonists (LABAs) exert other effects such as inhibition of airway smooth-muscle cell proliferation and inflammatory mediator release as well as non smooth-muscle effects such as stimulation of mucociliary transport, cytoprotection of the respiratory mucosa and attenuation of neutrophil recruitment and activation.
Further, use of a long acting β2-agonist reduces the frequency of drug administration.
Currently available long acting β2-agonists (LABAs) include salmeterol and formoterol.
Even though it is known that β2-agonists provide a symptomatic relief in bronchoconstriction and another component of asthma, which is inflammation, requires separate treatment such as steroid. Most of the inhaled corticosteroids need to be administered in multiple dosage regimens.
Corticosteroids exhibit inhibitory effects on inflammatory cells and inflammatory mediators involved in the pathogenesis of respiratory disorders. Treatment with a corticosteroid/glucocorticoid is considered one of the most potent and effective therapies currently available for persistent asthma.
But the use of corticosteroids has been limited due to potential side effects. The side effects that are normally feared with corticosteroids include suppression of the Hypothalamic-Pituitary-Adrenal (HPA) axis, effects on bone growth in children and on bone density in the elderly, ocular complications (cataract formation and glaucoma) and skin atrophy.
Currently available corticosteroids include beclomethasone, budesonide, fluticasone, mometasone, ciclesonide and triamcinolone.
Currently, there are several approved combinations of long-acting β-agonist (LABA) and inhaled corticosteroid (ICS). Some of these approved combinations for the treatment of asthma and chronic obstructive pulmonary disease (COPD) are salmeterol/fluticasone propionate (Advair diskus, Advair HFA), and formoterol fumarate dihydrate/budesonide (Symbicort).
Combination therapy of a long-acting β-agonist (LABA) with an inhaled corticosteroid (ICS) improves pulmonary efficiency, reduces inflammatory response and provides symptomatic relief as compared to higher doses of inhaled corticosteroid (ICS) alone in patients affected by respiratory disorders such as asthma and COPD.
Additionally it simplifies the therapy, reduces the cost and also provides control of respiratory disorders.
U.S. Pat. No. 6,030,604 discloses a dry powder composition comprising glucocorticoids and β2-agonist.
WO0178745 discloses compositions containing a combination of formoterol and fluticasone propionate.
U.S. Pat. No. 7,172,752 discloses inhalation particles comprising a combination of a β2-agonist and a glucocorticosteroid in a predetermined and constant ratio.
WO02083113 discloses pharmaceutical compositions comprising formoterol and a steroidal anti-inflammatory agent in a pharmacologically suitable fluid.
WO2004028545 discloses a combination of a long-acting β2-agonist and a glucocorticosteroid in the treatment of fibrotic diseases.
US 2005053553 discloses methods for administration by inhalation of a metered dry powder having combined doses of formoterol and fluticasone.
Further, none of the above mentioned prior arts disclose a specific combination of Arformoterol and Fluticasone furoate
Most of the available combinations of a long-acting β-agonist (LABA) with inhaled corticosteroid (ICS) have to be administered twice daily.
Even from the patient compliance point of view, the treatment requires for the patient to comply with different dosage regimens, different frequencies of administration etc.
Efforts to improve compliance have been aimed at by simplifying the medication packaging, providing effective medication reminders, improving patient education and limiting the number of medications prescribed simultaneously.
Hence, there still remains a need to formulate a pharmaceutical composition which simplifies the dosage regimen by administering an effective combination of arformoterol and fluticasone furoate for the treatment of respiratory disorders.